Ritu Verma

Eosinophilic Esophagitis: A 10-Year Experience in 381 Children

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is a disorder characterized by a severe, isolated eosinophilic infiltration of the esophagus unresponsive to aggressive acid blockade but responsive to the removal of dietary antigens. We present information relating to our 10-year experience in children diagnosed with EoE. METHODS We conducted a retrospective study between January 1, 1994, and January 1, 2004, to evaluate all patients diagnosed with EoE. Clinical symptoms, demographic data, endoscopic findings, and the results of various treatment regimens were collected and evaluated. RESULTS A total of 381 patients (66% male, age 9.1 +/- 3.1 years) were diagnosed with EoE: 312 presented with symptoms of gastroesophageal reflux; 69 presented with dysphagia. Endoscopically, 68% of patients had a visually abnormal esophagus; 32% had a normal-appearing esophagus despite a severe histologic esophageal eosinophilia. The average number of esophageal eosinophils (per 400 x high power field) proximally and distally were 23.3 +/- 10.5 and 38.7 +/- 13.3, respectively. Corticosteroids significantly improved clinical symptoms and esophageal histology; however, upon their withdrawal, the symptoms and esophageal eosinophilia recurred. Dietary restriction or complete dietary elimination using an amino acid-based formula significantly improved both the clinical symptoms and esophageal histology in 75 and 172 patients, respectively. CONCLUSIONS Medications such as corticosteroids are effective; however, upon withdrawal, EoE recurs. The removal of dietary antigens significantly improved clinical symptoms and esophageal histology in 98% of patients.

14 years of eosinophilic esophagitis: clinical features and prognosis.

Objective: To determine the natural history of treated and untreated eosinophilic esophagitis (EE) and examine the presenting symptoms of EE. Patients and Methods: Retrospective and prospective chart review of all patients diagnosed with EE at The Childrens Hospital of Philadelphia. EE was defined as greater than 20 eosinophils per high power field after treatment with reflux medications. Results: We identified 620 patients in our database in the last 14 years and 330 patients with greater than 1 year of follow-up for analysis. The number of new EE patients has increased on an annual basis. Of the patients presenting with EE, 68% were younger than 6 years old. Reflux symptoms and feeding issues/failure to thrive were the most common presenting symptoms for EE. Eleven patients had resolution of all of their food allergies and 33 patients had resolutions of some of their food allergies. No patients have progression of EE into other gastrointestinal disorders. Conclusions: EE is a chronic disease with less than 10% of the population developing tolerance to their food allergies. EE does not progress into other gastrointestinal diseases.

Common variants at 5q22 associate with pediatric eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the accumulation of eosinophils in the esophagus. We report association of EoE with variants at chromosome 5q22 encompassing TSLP and WDR36 (rs3806932, combined P = 3.19 × 10−9). TSLP is overexpressed in esophageal biopsies from individuals with EoE compared with unaffected individuals, whereas WDR36 expression is unaltered between the two groups. These data implicate the 5q22 locus in the pathogenesis of EoE and identify TSLP as the most likely candidate gene in the region.

Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet.

BACKGROUND Eosinophilic esophagitis (EoE) is a chronic inflammatory disease with isolated eosinophils in the esophagus predominantly triggered by foods. The optimal testing to identify inciting foods remains unclear. OBJECTIVES We sought to determine the effectiveness of allergy testing-directed diets in patients with EoE. METHODS A retrospective analysis of all children with EoE seen at the Childrens Hospital of Philadelphia between 2000 and 2011 identified 941 patients with EoE. Skin prick tests (SPTs) and atopy patch tests (APTs) were conducted, and predictive values were calculated. IgE-mediated food reactions were also identified. A food was considered to cause EoE if its elimination led to resolution of esophageal eosinophilia or reintroduction led to reoccurrence of EoE. The effectiveness of the various elimination diets was compared with targeted food antigen elimination. RESULTS Definitive foods causing EoE were identified, with milk, egg, wheat, and soy as the most common foods in 319 patients. IgE-mediated reactions (urticaria and anaphylaxis) were seen in 15%. The negative predictive value for the combination of SPTs and APTs averaged 92%, with the exception of milk at 44%, and the positive predictive value averaged 44%. An empiric 6-food elimination diet or removal of positive foods on allergy testing (SPTs/APTs) both had a histologic success rate of 53%. Removal of foods identified on SPTs/APTs plus empiric elimination of milk leads to resolution in 77% of patients. CONCLUSION An elimination diet based on SPT/APT results leads to resolution of esophageal eosinophilia in a similar proportion of patients as empiric removal of foods but required that fewer foods be removed. These observations suggest that both methods are acceptable options.

Entropically driven self–assembly and interaction in suspension

In this paper we present fundamental studies elucidating the role of entropy in particle suspensions. We focus on systems composed of large colloidal particles along with a second, usually smaller species such as a particle or polymer. We describe direct measurements of these interactions in suspension, and we systematically show how these forces can be used to control the self–assembly of colloidal particles. The paper provides a unified review of the experiments from our laboratory, and in a few cases touches on very recent results.

Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn's disease in children.

Numerous adult studies show a 30-65% response rate to azathioprine (AZA) or 6-mercaptopurine (6-MP) for significant perianal Crohns disease. The aim of this study was to evaluate whether these drugs healed pediatric perianal Crohns disease. Records of pediatric Crohns patients were retrospectively reviewed for significant perianal disease treated with AZA or 6-MP for > or =6 months. The patients perianal disease was reviewed and evaluated for fistulas, drainage, induration, and tenderness. In addition, the patients were given a score using the Irvine Perianal Disease Activity Index (PDAI). Patients were retrospectively scored upon initiation of treatment and after six months of therapy. Possible scores ranged from 0-20. Twenty patients met the study criteria. Five patients were considered treatment failures. One patient required a colostomy after 1.5 months of therapy, one developed pancreatitis, and three were noncompliant with therapy. Of the remaining 15 patients who were treated for > or =6 months, 67% had an improvement in drainage, 73% in tenderness, 60% in induration, and 40% in fistula closure. The mean Irvine PDAI was 7.67 +/- 2.19 initially and 4.40 +/- 1.72 after six months of therapy. The improvement was statistically significant (p < 0.001). AZA and 6-MP are effective treatments for healing significant perianal Crohns disease in pediatrics.

Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients.

OBJECTIVES:Understanding cytokine production patterns in early mucosal lesions of pediatric patients newly diagnosed with inflammatory bowel disease (IBD) may be critical to understanding IBD pathogenesis. Interleukin-6 (IL-6) has a central role in a multitude of immune system reactions; however, inconsistent lamina propria and serum IL-6 has been reported in IBD patients. Newly diagnosed pediatric IBD patients have not previously been evaluated for lamina propria or serum IL-6.METHODS:Serum and intestinal lamina propria biopsy whole organ culture supernatants were evaluated by ELISA for IL-6 obtained from newly diagnosed IBD patients, before initiation of immunomodulatory therapies.RESULTS:Levels of lamina propria IL-6 demonstrated significant correlation with graded severity of histological inflammation (p < 0.001). Log-transformed serum and organ culture IL-6 levels demonstrated significant correlation (p < 0.0001, R2= 0.6226). Assigning a demarcation level of >400 pg/ml, serum IL-6 concentrations were a superior marker for the presence of microscopic intestinal inflammation than erythrocyte sedimentation rate (ESR), with a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 82%. When evaluating subtypes of IBD, serum IL-6 levels were correlated more significantly with active disease in ulcerative colitis patients (p = 0.01, R2= 0.74) than in Crohns disease patients (p = 0.21, R2= 0.33).CONCLUSIONS:This study outlines graded production of IL-6 in intestinal lamina propria and serum of newly diagnosed pediatric IBD patients, confirming the presence of IL-6 in early IBD patients. In addition, serum IL-6 may be a good predictor of IBD in pediatric patients with suspected or newly diagnosed IBD.

Bone Mineral Content Deficits of the Spine and Whole Body in Children at Time of Diagnosis With Celiac Disease

Background: The aim of this study was to determine whether children with celiac disease (CD) have deficits in spine (SP) and whole body (WB) bone mineral content (BMC) at time of diagnosis, and whether the deficits are related to altered growth and body composition. The secondary aim was to examine the effect of histological grade on BMC. Patients and Methods: A retrospective study of children who had undergone a dual energy x-ray absorptiometry scan at the time of diagnosis with CD between October 1, 2003, and June 15, 2006, were compared with a healthy reference sample of similar age and race from the same geographic region in the United States. SP and WB BMC were expressed as sex-specific z scores relative to age and relative to height to assess differences in the CD group versus controls. Pearson correlation, t tests, and analysis of variance were performed to determine predictors of BMC. Results: Forty-four children (mean age 10.6 ± 3.4 years; 77% female, 96% white) with CD were evaluated and compared with 338 healthy children. Children with CD were shorter than children of similar age and sex. SP and WB BMC for age z scores were significantly lower in the CD group compared with controls. When adjusted for height, significant deficits in WB BMC persisted in patients with CD. Low SP and WB BMC correlated with advanced histological grade in CD. Low body mass index correlated with low WB BMC in CD. Conclusions: Newly diagnosed children with CD may benefit from screening for low bone mineral content. Patients with low body mass index and those with advanced histological damage (Marsh grade IIIc) particularly may be at risk for osteopenia.

Lymphocytic gastritis in pediatric celiac disease.

An increase in gastric intraepithelial lymphocytes has been observed in some patients with the typical small intestinal changes of celiac disease. To date, no clinical parameters have been described that identify the subset of patients more likely to have gastric involvement. In this study we compared the clinical features of celiac disease patients with and without lymphocytic gastritis to determine if the presence of gastric involvement at diagnosis portends a more severe form of celiac disease. We reviewed the pathology reports and hematoxylin and eosin-stained slides of 304 patients with biopsy-proven celiac disease diagnosed over an 11-year period. Thirty-nine of these patients had lymphocytic gastritis. Compared to patients without gastric involvement, those with lymphocytic gastritis were statistically more likely to be diagnosed at an earlier age and present with more profound laboratory findings and duodenal mucosal damage compared to patients with celiac disease without gastric involvement. These findings indicate that in the pediatric population, the presence of lymphocytic gastritis in celiac disease defines a unique group of patients with more severe disease (by clinical and laboratory measures) at the time of diagnosis.

NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders.

Dietary exclusion of gluten-containing products has become increasingly popular in the general population, and currently ∼30% of people in the United States are limiting gluten ingestion. Although celiac disease (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS) constitute a spectrum of gluten-related disorders that require exclusion of gluten from the diet, together these account for a relatively small percentage of those following a gluten-free diet, and the vast majority has no medical necessity for doing so. Differentiating between CD, WA, and NCGS has important prognostic and therapeutic implications. Because of the protean manifestations of gluten-related disorders, it is not possible to differentiate between them on clinical grounds alone. This clinical report will compare and contrast the manifestations of gluten-related disorders, emphasize the importance of differentiating between these conditions, discuss initial and subsequent tests needed to confirm the diagnosis, and provide recommendations on treatment and follow-up for each condition.